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Heat-stable enterotoxin A3/A4 (ST-H) (ST-IB) (STA3/STA4) (Linaclotide)

 HST3_ECOLX              Reviewed;          72 AA.
P07965; P26588;
01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
15-DEC-1998, sequence version 3.
22-NOV-2017, entry version 64.
RecName: Full=Heat-stable enterotoxin A3/A4;
AltName: Full=ST-H;
AltName: Full=ST-IB;
AltName: Full=STA3/STA4;
AltName: INN=Linaclotide;
Flags: Precursor;
Name=sta3; Synonyms=sta4;
Escherichia coli.
Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
Enterobacteriaceae; Escherichia.
NCBI_TaxID=562;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=3071819; DOI=10.1016/0147-619X(88)90006-6;
Stieglitz H., Cervantes L., Robledo R., Fonseca R., Covarrubias L.,
Bolivar F., Kupersztoch Y.M.;
"Cloning, sequencing, and expression in Ficoll-generated minicells of
an Escherichia coli heat-stable enterotoxin gene.";
Plasmid 20:42-53(1988).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=153837-2;
PubMed=6341230;
Moseley S.L., Hardy J.W., Huq M.I., Echeverria P., Falkow S.;
"Isolation and nucleotide sequence determination of a gene encoding a
heat-stable enterotoxin of Escherichia coli.";
Infect. Immun. 39:1167-1174(1983).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2190361; DOI=10.1016/0041-0101(90)90085-L;
Zhou X., Shen L.P., Chi C.W.;
"Isolation and nucleotide sequence determination of a gene encoding a
heat-stable enterotoxin of Escherichia coli.";
Toxicon 28:453-456(1990).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2643580;
Guzman-Verduzio L.M., Kupersztoch Y.M.;
"Rectification of two Escherichia coli heat-stable enterotoxin allele
sequences and lack of biological effect of changing the carboxy-
terminal tyrosine to histidine.";
Infect. Immun. 57:645-648(1989).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=2680769; DOI=10.1016/0378-1119(89)90182-0;
Dwarakanath P., Visweswariah S.S., Subrahmanyam Y.V.B.K., Shanthi G.,
Jagannatha H.M., Balganesh T.S.;
"Cloning and hyperexpression of a gene encoding the heat-stable toxin
of Escherichia coli.";
Gene 81:219-226(1989).
[6]
PROTEIN SEQUENCE OF 54-72.
PubMed=6759126; DOI=10.1111/j.1432-1033.1982.tb07047.x;
Aimoto S., Takao T., Shimonishi Y., Hara S., Takeda T., Takeda Y.,
Miwatani T.;
"Amino-acid sequence of a heat-stable enterotoxin produced by human
enterotoxigenic Escherichia coli.";
Eur. J. Biochem. 129:257-263(1982).
[7]
DISULFIDE BONDS.
PubMed=3552731; DOI=10.1016/0014-5793(87)80134-5;
Shimonishi Y., Hidaka Y., Koizumi M., Hane M., Aimoto S., Takeda T.,
Miwatani T., Takeda Y.;
"Mode of disulfide bond formation of a heat-stable enterotoxin (STh)
produced by a human strain of enterotoxigenic Escherichia coli.";
FEBS Lett. 215:165-170(1987).
[8]
PROTEOLYTIC PROCESSING.
PubMed=2187146; DOI=10.1111/j.1365-2958.1990.tb00593.x;
Rasheed J.K., Guzman-Verduzco L.M., Kupersztoch Y.M.;
"Two precursors of the heat-stable enterotoxin of Escherichia coli:
evidence of extracellular processing.";
Mol. Microbiol. 4:265-273(1990).
-!- FUNCTION: Toxin which activates the particulate form of guanylate
cyclase and increases cyclic GMP levels within the host intestinal
epithelial cells.
-!- SUBCELLULAR LOCATION: Secreted.
-!- PHARMACEUTICAL: Linaclotide is under clinical trial by Microbia to
be used to improve bowel function in patients with chronic
constipation. Linaclotide corresponds to residues 59 to 72 with
Tyr-62.
-!- SIMILARITY: Belongs to the heat-stable enterotoxin family.
{ECO:0000305}.
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EMBL; J03311; AAA24652.1; -; Genomic_DNA.
EMBL; M34916; AAA23990.1; -; Genomic_DNA.
EMBL; M18346; AAA23730.1; -; Genomic_DNA.
EMBL; M29255; AAA24686.1; -; Genomic_DNA.
PIR; JS0292; QHECIB.
PIR; JT0373; QHEC4.
RefSeq; WP_013188501.1; NZ_NIEW01000146.1.
RefSeq; YP_008531452.1; NC_022333.1.
GeneID; 16833876; -.
GO; GO:0005615; C:extracellular space; IEA:InterPro.
GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
InterPro; IPR019806; Heat-stable_enterotox_CS.
InterPro; IPR001489; Heat-stable_enterotox_STa.
Pfam; PF02048; Enterotoxin_ST; 1.
PROSITE; PS00273; ENTEROTOXIN_H_STABLE; 1.
1: Evidence at protein level;
Direct protein sequencing; Disulfide bond; Enterotoxin;
Pharmaceutical; Secreted; Signal; Toxin.
SIGNAL 1 19
PROPEP 20 53 {ECO:0000269|PubMed:6759126}.
/FTId=PRO_0000035130.
PEPTIDE 54 72 Heat-stable enterotoxin A3/A4.
/FTId=PRO_0000035131.
DISULFID 59 64 {ECO:0000269|PubMed:3552731}.
DISULFID 60 68 {ECO:0000269|PubMed:3552731}.
DISULFID 63 71 {ECO:0000269|PubMed:3552731}.
CONFLICT 19 19 A -> P (in Ref. 2; AAA23990).
{ECO:0000305}.
SEQUENCE 72 AA; 7909 MW; 1C5C9292BFCBA6BA CRC64;
MKKSILFIFL SVLSFSPFAQ DAKPVESSKE KITLESKKCN IAKKSNKSGP ESMNSSNYCC
ELCCNPACTG CY


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